Shields' first novel, Heroes, was published in 1984. From 1985 to 1988, he was a visiting assistant professor at St. Lawrence University in Canton, New York. In 1989, he published his second novel, Dead Languages, a book about a boy who stutters so badly that he worships words. Shields' third book, Handbook for Drowning: A Novel in Stories (1992), marked the beginning of his shift from traditional literary fiction toward collage, the blurring of genres, essay, and autobiography. This shift continued and deepened in such books as Remote: Reflections on Life in the Shadow of Celebrity (1996), Black Planet: Facing Race During an NBA Season (1999), Enough About You: Notes Toward the New Autobiography (2002), and The Thing About Life Is That One Day You'll Be Dead (2008). Shields' next book, Reality Hunger: A Manifesto (Knopf, 2010), argues for the obliteration of distinctions between genres, the overturning of laws regarding appropriation, and the creation of new forms for a new millennium.

Much of Shields' work embodies and enacts a critique of traditional categories within art and culture, such as the boundary between fiction and nonfiction; for instance, in Reality Hunger, in which he argues for the abandonment of the traditional novelistic form because of its inadequacy in dealing with what he views as an increasingly fragmentary culture. Shields writes, "I find it very nearly impossible to read a contemporary novel that presents itself unselfconsciously as a novel, since it's not clear to me how such a book could convey what it feels like to be alive right now." In its place, he advocates "collage" forms such as the lyric essay, prose poetry, and the "anti-novel, built from scraps."[3]

Shields' books have generally been published to wide acclaim. Remote: Reflections on Life in the Shadow of Celebrity received the PEN/Revson Award. Black Planet: Facing Race During an NBA Season, a finalist for the National Book Critics Circle Award and PEN USA Award, was named one of 1999's ten best books of non-fiction by Esquire, Newsday, Los Angeles Weekly, and Amazon.com. In Newsday, A. O. Scott called it "one of the best books ever written on the subject of sport in America, which is to say a book that is about a great deal more than sport." Reality Hunger was named one of the best books of 2010 by more than thirty publications.

Reality Hunger was received with a polarized mixture of excitement and criticism. In the New York Times Book Review, Luc Sante wrote that "Reality Hunger urgently and succinctly addresses matters that have been in the air, have relentlessly gathered momentum, and have just been waiting for someone to link them together... [Shields'] book probably heralds what will be the dominant modes in years and decades to come."[4]

In The New Yorker, James Wood criticized the book as being "imprecise", arguing that its privileging of "reality" over traditional fiction was "highly problematic." However, he conceded that Shields' arguments about the "tediousness and terminality of current fictional convention are well-taken."[5]

Shields' How Literature Saved My Life (Knopf), was published by Knopf on February 5, 2013. In a review in Boston Globe, Eugenia Williamson wrote, "In this wonderful, vastly entertaining book, he weaves together literary criticism, quotations, and his own fragmentary recollections to illustrate, in form and content, how art — real art, the kind that engages and reflects the world around it — has made his life meaningful as both creator and beholder." [6] In New Statesman, Max Liu found fault with Shields' artistic stance, writing, "Shields' books yearn for meaning but they're as mediated by performance as the culture they criticise. Shields relishes his role as controversialist ('Fine by me') and his weakness is less writing to please admirers than to deflect detractors."[7]

In September 2013, the oral biography Salinger was published; Shields and Shane Salerno are the book's co-authors. In The Washington Post, Louis Bayard called Salinger "the thorny, complicated portrait that its thorny, complicated subject deserves." In The Sunday Times (London), John Walsh wrote, "I predict with the utmost confidence that, after this, the world will not need another Salinger biography."